Cardiac microtissues from human pluripotent stem cells recapitulate the phenotype of long-QT syndrome
| Autor: | Elisa Giacomelli, Luca Sala, Dorien Ward-van Oostwaard, Milena Bellin |
|---|---|
| Přispěvatelé: | Giacomelli, E, Sala, L, Oostwaard, D, Bellin, M |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Chronotropic
Cell type Long QT syndrome Induced Pluripotent Stem Cells Biophysics 030204 cardiovascular system & hematology Biology Long-QT syndrome Biochemistry Multi-electrode array Human pluripotent stem cell cardiomyocyte 03 medical and health sciences 0302 clinical medicine medicine Humans Myocytes Cardiac Human Induced Pluripotent Stem Cells Induced pluripotent stem cell Molecular Biology Cells Cultured 030304 developmental biology 0303 health sciences Cell Biology medicine.disease Phenotype 3. Good health Cell biology Long QT Syndrome Electrophysiology Drug screening Cardiac microtissue |
| Zdroj: | Biochemical and Biophysical Research Communications Biochemical and Biophysical Research Communications, 572, 118-124. ACADEMIC PRESS INC ELSEVIER SCIENCE |
| Popis: | Background: Human induced pluripotent stem cells (hiPSCs) and their derivative cardiomyocytes (hiPSCCMs) have been successfully used to study the electrical phenotype of cardiac ion channel diseases. However, strategies to mature CMs and more comprehensive systems recapitulating the heart complexity are required to advance our ability to capture adult phenotypes. Methods: We differentiated wild-type (WT) and long QT syndrome type 1 (LQT1) hiPSCs into CMs, endothelial cells and cardiac fibroblasts. The three cell types were combined to form three-dimensional (3D) spheroids, termed "cardiac microtissues" (cMTs) and the electrophysiological properties were measured using 96-well multi-electrode arrays. Results: LQT1 cMTs displayed prolonged field potential duration compared to WT controls, thus recapitulating the typical feature of LQTS. Isoprenaline caused a positive chronotropic effect on both LQT1 and WT cMTs. The 96-well multi-electrode array format proved suitable to detect electrical changes directly in the 3D tissues. Conclusions: 3D hiPSC cMTs are a scalable tool that can be used to identify LQT electrical hallmarks and drug responses. We anticipate this tool can be adopted by pharmaceutical companies to screen cardioactive compounds. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Databáze: | OpenAIRE |
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